scholarly journals Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Antoinette Bugyei-Twum ◽  
Armin Abadeh ◽  
Kerri Thai ◽  
Yanling Zhang ◽  
Melissa Mitchell ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diastolic Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Cardiac Fibrosis ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals NLRP3 Inflammasome Activation in Dialyzed Chronic Kidney Disease Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0122272 ◽  
Author(s):  
Simona Granata ◽  
Valentina Masola ◽  
Elisa Zoratti ◽  
Maria Teresa Scupoli ◽  
Anna Baruzzi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Relief of Pressure Overload in Mice

2020 ◽  
Vol 34 (5) ◽  
pp. 629-640
Author(s):  
Xueling Li ◽  
Qin Zhu ◽  
Qingcheng Wang ◽  
Qinggang Zhang ◽  
Yaru Zheng ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Myocardial Cell ◽  
Heart Weight ◽  
Inflammasome Activation ◽  
Clinical Prognosis ◽  
Nlrp3 Inflammasome Activation ◽  
Neprilysin Inhibitor

Abstract Background/aims The persistent existence of pathological cardiac remodeling, resulting from aortic stenosis, is related to poor clinical prognosis after successful transcatheter aortic valve replacement (TAVR). Sacubitril/valsartan (Sac/Val), comprising an angiotensin receptor blocker and a neprilysin inhibitor, has been demonstrated to have a beneficial effect against pathological cardiac remodeling, including cardiac fibrosis and inflammation in heart failure. The aim of this study was to determine whether Sac/Val exerts a cardioprotective effect after pressure unloading in mice. Methods and results Male C57BL/6 J mice were subjected to debanding (DB) surgery after 8 weeks (wk) of aortic banding (AB). Cardiac function was assessed by echocardiography, which indicated a protective effect of Sac/Val after DB. After treatment with Sac/Val post DB, decreased heart weight and myocardial cell size were observed in mouse hearts. In addition, histological analysis, immunofluorescence, and western blot results showed that Sac/Val attenuated cardiac fibrosis and inflammation after DB. Finally, our data indicated that Sac/Val treatment could significantly suppress NF-κB signaling and NLRP3 inflammasome activation in mice after relief of pressure overload. Conclusion Sac/Val exerted its beneficial effects to prevent maladaptive cardiac fibrosis and dysfunction in mice following pressure unloading, which was at least partly due to the inhibition of NLRP3 inflammasome activation.

scholarly journals Therapeutic Effect of Endothelin-Converting Enzyme Inhibitor on Chronic Kidney Disease through the Inhibition of Endoplasmic Reticulum Stress and the NLRP3 Inflammasome

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 398
Author(s):  
Yung-Ho Hsu ◽  
Cai-Mei Zheng ◽  
Chu-Lin Chou ◽  
Yi-Jie Chen ◽  
Yu-Hsuan Lee ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Epithelial Cells ◽  
Er Stress ◽  
Nlrp3 Inflammasome ◽  
Enzyme Inhibitor ◽  
Inflammasome Activation ◽  
Tubular Epithelial Cells ◽  
Domain 3

Chronic inflammation and oxidative stress significantly contribute to the development and progression of chronic kidney disease (CKD). The NOD-like receptor family pyrin containing domain-3 (NLRP3) inflammasome plays a key role in the inflammatory response. The renal endothelin (ET) system is activated in all cases of CKD. Furthermore, ET-1 promotes renal cellular injury, inflammation, fibrosis and proteinuria. Endothelin-converting enzymes (ECEs) facilitate the final processing step of ET synthesis. However, the roles of ECEs in CKD are not clear. In this study, we investigated the effects of ETs and ECEs on kidney cells. We found that ET-1 and ET-2 expression was significantly upregulated in the renal tissues of CKD patients. ET-1 and ET-2 showed no cytotoxicity on human kidney tubular epithelial cells. However, ET-1 and ET-2 caused endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation in tubular epithelial cells. The ECE inhibitor phosphoramidon induced autophagy. Furthermore, phosphoramidon inhibited ER stress and the NLRP3 inflammasome in tubular epithelial cells. In an adenine diet-induced CKD mouse model, phosphoramidon attenuated the progression of CKD by regulating autophagy, the NLRP3 inflammasome and ER stress. In summary, these findings showed a new strategy to delay CKD progression by inhibiting ECEs through autophagy activation and restraining ER stress and the NLRP3 inflammasome.

scholarly journals Nlrp3 Deficiency Alleviates Angiotensin II-Induced Cardiomyopathy by Inhibiting Mitochondrial Dysfunction

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yu Chen ◽  
Meiying Zeng ◽  
Yang Zhang ◽  
Hui Guo ◽  
Wei Ding ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Gene Deletion ◽  
Cardiac Fibrosis ◽  
Inflammasome Activation ◽  
Ang Ii ◽  
Nlrp3 Gene ◽  
Nlrp3 Inflammasome Activation

Inflammation has been considered a key component in the pathogenesis and progression of angiotensin II- (Ang II-) induced cardiac hypertrophy and related cardiomyopathy. As a vital mediator of inflammation, the role of the Nlrp3 inflammasome in Ang II-induced cardiomyopathy remains unclear. This study was aimed to determine whether Nlrp3 inflammasome activation and its downstream pathway were involved in Ang II-induced cardiomyopathy. We established an Ang II infusion model in both wild-type and Nlrp3-/- mice to determine the contribution of Nlrp3 to cardiac function. Cardiac fibrosis was determined by Masson’s trichrome staining, real-time PCR, and TUNEL assay; cardiac function was assessed by echocardiography. Nlrp3 inflammasome activation and related downstream cytokines were measured by Western blotting and enzyme-linked immunosorbent assays; mitochondrial dysfunction was examined by transmission electron microscopy and real-time PCR. We found that Ang II-infused mice showed impaired cardiac function, as evidenced by increased cardiac fibrosis, apoptosis, inflammation, and left ventricular dysfunction. However, these alterations were significantly alleviated in the mice with Nlrp3 gene deletion. Moreover, Ang II-infused mice showed increased Nlrp3 inflammasome activity relative to that of the cytokines IL-1β and IL-18, increased reactive oxygen species, mitochondrial abnormalities, and decreased mtDNA copy number and ATP synthase activity. These molecular and pathological alterations were also attenuated in Nlrp3 deficient mice. In conclusion, Nlrp3 inflammasome-induced mitochondrial dysfunction is involved in Ang II-induced cardiomyopathy. Nlrp3 gene deletion attenuated mitochondrial abnormalities, cardiac inflammation, oxidative stress, and fibrosis and thus alleviated heart dysfunction and hypertrophy. Targeting the Nlrp3 inflammasome and/or mitochondria may be a therapeutic approach for Ang II-induced cardiac diseases.

scholarly journals Intermedin1-53 Inhibits NLRP3 Inflammasome Activation by Targeting IRE1α in Cardiac Fibrosis

2021 ◽  
Author(s):  
Lin-Shuang Zhang ◽  
Jin-Sheng Zhang ◽  
Yue-Long Hou ◽  
Wei-Wei Lu ◽  
Xian-Qiang Ni ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Cardiac Fibrosis ◽  
Underlying Mechanism ◽  
Inflammasome Activation ◽  
Rat Myocardium ◽  
Ang Ii ◽  
Receptor System ◽  
Nlrp3 Inflammasome Activation ◽  
Pka Pathway

Abstract Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributed to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigates cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) was found in Ang II treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3 and anti-fibrotic response. In conclusion, IMD alleviates cardiac fibrosis by inhibiting NLRP3 inflammasome activation via suppressing IRE1α and cAMP/PKA pathway.

scholarly journals NLRP3 Inflammasome Activation Confers Resistance to Loop Diuretics in Proteinuric Kidney Disease

2015 ◽  
Vol 17 (2) ◽  
pp. S86
Author(s):  
Wei Gong ◽  
Yibo Zhuang ◽  
Guixia Ding ◽  
Songming Huang ◽  
Zhanjun Jia ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Nlrp3 Inflammasome ◽  
Loop Diuretics ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation
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